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Toxicological information

Acute Toxicity: inhalation

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Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1976
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: This study is rated "reliable with restrictions" because this study was not conducted according to GLP, but was conducted similar to OECD TG 403, with deviations.
Justification for type of information:
A discussion and report on the read across strategy is given as an attachment in Section 13.
Cross-reference
Reason / purpose:
read-across: supporting information
Reference
Endpoint:
acute toxicity: inhalation
Type of information:
read-across based on grouping of substances (category approach)
Adequacy of study:
key study
Study period:
1976
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: This study is rated "reliable with restrictions" because this study was not conducted according to GLP, but was conducted similar to OECD TG 403, with deviations.
Justification for type of information:
A discussion and report on the read across strategy is given as an attachment in Section 13.
Reason / purpose:
read-across source
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
yes
Remarks:
Animals were exposed for 6 hours versus 4 hours as outlined in the guidance
GLP compliance:
no
Test type:
standard acute method
Species:
rat
Strain:
Sprague-Dawley
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Breeding Laboratory
- Age at study initiation: Not provided
- Weight at study initiation: 175 to 200 grams
- Fasting period before study: Data not provided
- Housing: Animals were housed in groups of five.
- Diet (e.g. ad libitum): Purina Cubed diet, ad libitum
- Water (e.g. ad libitum): Tap water, ad libitum
- Acclimation period: 7 days
Route of administration:
inhalation: vapour
Type of inhalation exposure:
other: Specific exposure information is not provided. An assessment of the information provided in the report indicates that the whole animal was placed in the exposure chamber
Vehicle:
other: Air
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure chamber volume: 112 Litres
- Method of holding animals in test chamber: Data not provided
- Source and rate of air: 15 L/min


TEST ATMOSPHERE
- Brief description of analytical method used: The nominal concentration of the test chemical was determined based on the weight of the material used during 360 minutes with an airflow of 40L/min.
- Samples taken from breathing zone: No








Analytical verification of test atmosphere concentrations:
no
Duration of exposure:
ca. 6 h
Concentrations:
Nominal concentration of the test material was determined to be 28 mg/L.

No. of animals per sex per dose:
10 males
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: All animals were observed during exposure and daily thereafter until study termination; animals were weighed prior to exposure and on day 7 and day 14.
- Necropsy of survivors performed: Yes
- Other examinations performed: Clinical signs, body weight, and histopathology
Statistics:
Statistical analysis, if performed, is not provided in the study report.
Sex:
male
Dose descriptor:
other: LT50
Effect level:
ca. 265 other: minutes
Exp. duration:
6 h
Remarks on result:
other: LT50 data is for rats.
Mortality:
All ten rats died during the six hour exposure duration.
Clinical signs:
other: Rats exhibited hypoactivity and dyspnoea at 45 minutes of exposure. The sequence of events included hyperactivity, hypoactivity, ataxia, salivation, dyspnoea, tremors, tonic or clonic-tonic convulsions interspersed with periods of mortality. Rats also ex
Body weight:
All control animals and surviving animals gained body weight in a normal manner during the post exposure period.

Gross pathology:
Animals that died during the exposure consistently showed moderate to severe haemorrhage in large areas of the lungs. Rats also exhibited extremely dark livers. Control animals sacrificed at study termination also exhibited a slight incidence of dark foci in the lungs.

Several toxicological effects including death were observed during the 6 hour exposure period. All ten rats died during the 6 hours exposure period. Rats exhibited hypoactivity and dyspnoea at 45 minutes of exposure. The sequence of events included hyperactivity, hypoactivity, ataxia, salivation, dyspnoea, tremors, tonic or clonic-tonic convulsions interspersed with periods of mortality. Rats also exhibited clonic convulsions and fasiculations. All control animals and surviving animals gained body weight in a normal manner during the post exposure period. Animals that died during the exposure consistently showed moderate to severe haemorrhage in large areas of the lungs. Rats also exhibited extremely dark livers. Control animals sacrificed at study termination also exhibited a slight incidence of dark foci in the lungs.

Interpretation of results:
other:
Remarks:
Not classified
Conclusions:
All ten rats died during the six hour exposure period. Based on this mortality data, it may be inferred that the test material is lethal to male Sprague-Dawley rats a concentration of 28 mg/L.
Executive summary:

In an acute inhalation toxicity assay, ten male Sprague-Dawley rats were exposed to nonene vapours for six hours. All animals were weighed prior to exposure and again on day 7 and 14. Animals were observed for gross signs of toxicity during exposure and daily until study termination. Surviving animals were sacrificed at study termination and all animals, including animals that died prior to study termination, were necropsied and all organs were examined for macroscopic changes. Lungs, kidneys, liver and trachea were stored for histopathological examination if needed. 

 Several toxicological effects including death were observed during the 6 hour exposure period. All ten rats died during the 6 hours exposure period. Rats exhibited hypoactivity and dyspnoea at 45 minutes of exposure. The sequence of events included hyperactivity, hypoactivity, ataxia, salivation, dyspnoea, tremors, tonic or clonic-tonic convulsions interspersed with periods of mortality. Rats also exhibited clonic convulsions and fasiculations. All control animals and surviving animals gained body weight in a normal manner during the course of the study. Animals that died during the exposure consistently showed moderate to severe haemorrhage in large areas of the lungs. Rats exhibited extremely dark livers. Control animals sacrificed at study termination also exhibited a slight incidence of dark foci in the lungs. Based on the mortality data, it may be inferred that the test material is lethal to rats at a concentration of 28 mg/L. The study authors reported a LT50 of 265 minutes for rats.

 

This study received a Klimisch score of 2 and is classified as “reliable with restrictions” because this study was not conducted according to GLP, but was conducted similar to OECD TG 403, with deviations.

 

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1976
Report Date:
1976

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
yes
Remarks:
Animals were exposed for 6 hours versus 4 hours as outlined in the guidance
GLP compliance:
no
Test type:
standard acute method

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Nonene MRD-76-42
- Substance type: Alkenes, C8-10-branched, C9-rich
- Physical state: Clear liquid with aromatic odour

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Breeding Laboratory
- Age at study initiation: Not provided
- Weight at study initiation: 175 to 200 grams
- Fasting period before study: Data not provided
- Housing: Animals were housed in groups of five.
- Diet (e.g. ad libitum): Purina Cubed diet, ad libitum
- Water (e.g. ad libitum): Tap water, ad libitum
- Acclimation period: 7 days

Administration / exposure

Route of administration:
inhalation: vapour
Type of inhalation exposure:
other: Specific exposure information is not provided. An assessment of the information provided in the report indicates that the whole animal was placed in the exposure chamber
Vehicle:
other: Air
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure chamber volume: 112 Litres
- Method of holding animals in test chamber: Data not provided
- Source and rate of air: 15 L/min


TEST ATMOSPHERE
- Brief description of analytical method used: The nominal concentration of the test chemical was determined based on the weight of the material used during 360 minutes with an airflow of 40L/min.
- Samples taken from breathing zone: No








Analytical verification of test atmosphere concentrations:
no
Duration of exposure:
ca. 6 h
Concentrations:
Nominal concentration of the test material was determined to be 28 mg/L.

No. of animals per sex per dose:
10 males
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: All animals were observed during exposure and daily thereafter until study termination; animals were weighed prior to exposure and on day 7 and day 14.
- Necropsy of survivors performed: Yes
- Other examinations performed: Clinical signs, body weight, and histopathology
Statistics:
Statistical analysis, if performed, is not provided in the study report.

Results and discussion

Effect levels
Sex:
male
Dose descriptor:
other: LT50
Effect level:
ca. 265 other: minutes
Exp. duration:
6 h
Remarks on result:
other: LT50 data is for rats.
Mortality:
All ten rats died during the six hour exposure duration.
Clinical signs:
other: Rats exhibited hypoactivity and dyspnoea at 45 minutes of exposure. The sequence of events included hyperactivity, hypoactivity, ataxia, salivation, dyspnoea, tremors, tonic or clonic-tonic convulsions interspersed with periods of mortality. Rats also ex
Body weight:
All control animals and surviving animals gained body weight in a normal manner during the post exposure period.

Gross pathology:
Animals that died during the exposure consistently showed moderate to severe haemorrhage in large areas of the lungs. Rats also exhibited extremely dark livers. Control animals sacrificed at study termination also exhibited a slight incidence of dark foci in the lungs.

Any other information on results incl. tables

Several toxicological effects including death were observed during the 6 hour exposure period. All ten rats died during the 6 hours exposure period. Rats exhibited hypoactivity and dyspnoea at 45 minutes of exposure. The sequence of events included hyperactivity, hypoactivity, ataxia, salivation, dyspnoea, tremors, tonic or clonic-tonic convulsions interspersed with periods of mortality. Rats also exhibited clonic convulsions and fasiculations. All control animals and surviving animals gained body weight in a normal manner during the post exposure period. Animals that died during the exposure consistently showed moderate to severe haemorrhage in large areas of the lungs. Rats also exhibited extremely dark livers. Control animals sacrificed at study termination also exhibited a slight incidence of dark foci in the lungs.

Applicant's summary and conclusion

Interpretation of results:
other:
Remarks:
Not classified
Conclusions:
All ten rats died during the six hour exposure period. Based on this mortality data, it may be inferred that the test material is lethal to male Sprague-Dawley rats a concentration of 28 mg/L.
Executive summary:

In an acute inhalation toxicity assay, ten male Sprague-Dawley rats were exposed to nonene vapours for six hours. All animals were weighed prior to exposure and again on day 7 and 14. Animals were observed for gross signs of toxicity during exposure and daily until study termination. Surviving animals were sacrificed at study termination and all animals, including animals that died prior to study termination, were necropsied and all organs were examined for macroscopic changes. Lungs, kidneys, liver and trachea were stored for histopathological examination if needed. 

 Several toxicological effects including death were observed during the 6 hour exposure period. All ten rats died during the 6 hours exposure period. Rats exhibited hypoactivity and dyspnoea at 45 minutes of exposure. The sequence of events included hyperactivity, hypoactivity, ataxia, salivation, dyspnoea, tremors, tonic or clonic-tonic convulsions interspersed with periods of mortality. Rats also exhibited clonic convulsions and fasiculations. All control animals and surviving animals gained body weight in a normal manner during the course of the study. Animals that died during the exposure consistently showed moderate to severe haemorrhage in large areas of the lungs. Rats exhibited extremely dark livers. Control animals sacrificed at study termination also exhibited a slight incidence of dark foci in the lungs. Based on the mortality data, it may be inferred that the test material is lethal to rats at a concentration of 28 mg/L. The study authors reported a LT50 of 265 minutes for rats.

 

This study received a Klimisch score of 2 and is classified as “reliable with restrictions” because this study was not conducted according to GLP, but was conducted similar to OECD TG 403, with deviations.